Stamp Lincon A, Obermayr Florian, Pontell Louise, Young Heather M, Xie Dan, Croaker David H, Song Zan-Min, Furness John B
Department of Anatomy and Neuroscience, University of Melbourne, Parkville, VIC, Australia.
Department of Pediatric Surgery and Pediatric Urology, University Children's Hospital Tuebingen, Tuebingen, Germany.
J Neurogastroenterol Motil. 2015 Oct 1;21(4):552-9. doi: 10.5056/jnm15079.
BACKGROUND/AIMS: Rats with a spontaneous null mutation in endothelin receptor type B or Ednrb (sl/sl; spotting lethal) lack enteric neurons in the distal bowel and usually die within the first week after birth. This early postnatal lethality limits their use for examining the potential of cell therapy to treat Hirschsprung disease, and for studies of the influence of EDNRB on the mature CNS and vascular systems.
We have developed a surgical intervention to prolong the life of the spotting lethal sl/sl rat, in which we perform a colostomy on postnatal (P) day 4-6 rats to avoid the fatal obstruction caused by the lack of colonic enteric neurons.
The stomas remained patent and functional and the rats matured normally following surgery. Weight gains were comparable between control and Hirschsprung phenotype (sl/sl) rats, which were followed until 4 weeks after surgery (5 weeks old). We confirmed the absence of enteric neurons in the distal colon of rats whose lives were saved by the surgical intervention.
This study provides a novel approach for studying EDNRB signalling in multiple organ systems in mature rats, including an animal model to study the efficacy of cell therapy to treat Hirschsprung disease.
背景/目的：内皮素B受体（Ednrb）发生自发无效突变的大鼠（sl/sl；斑点致死）在远端肠道缺乏肠神经元，通常在出生后第一周内死亡。这种出生后早期致死性限制了它们在研究细胞治疗先天性巨结肠病潜力以及研究EDNRB对成熟中枢神经系统和血管系统影响方面的应用。
我们开发了一种手术干预方法来延长斑点致死性sl/sl大鼠的寿命，即在出生后（P）第4 - 6天的大鼠身上进行结肠造口术，以避免因缺乏结肠肠神经元而导致的致命性梗阻。
术后造口保持通畅且功能正常，大鼠正常成熟。对照大鼠和先天性巨结肠表型（sl/sl）大鼠的体重增加情况相当，这些大鼠一直被跟踪到术后4周（5周龄）。我们证实了通过手术干预挽救生命的大鼠远端结肠中不存在肠神经元。
本研究为在成熟大鼠的多个器官系统中研究EDNRB信号传导提供了一种新方法，包括一种用于研究细胞治疗先天性巨结肠病疗效的动物模型。
